tbuckley/cabot-search huggingface dataset:
Progress Toward the Elimination of Mother-to-Child Transmission of Hepatitis B Virus — Worldwide, 2016–2021
Authors: Nino Khetsuriani, Olufunmilayo Lesi, Shalini Desai, Paige A. Armstrong, Rania A. Tohme
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

Mother-to-child transmission (MTCT) of hepatitis B virus (HBV) often results in chronic HBV infection, the leading cause of cirrhosis and liver cancer (1). If not vaccinated, nine in 10 children infected at birth will become chronically infected. Globally, an estimated 6.4 million (range = 4.4-10.8 million) children aged ≤5 years are living with chronic HBV infection (2). In 2016, the World Health Assembly endorsed the goal to eliminate viral hepatitis as a public health threat by 2030, including the elimination of MTCT of HBV (3). Elimination of MTCT of HBV can be validated by demonstrating ≤0.1% prevalence of HBV surface antigen (HBsAg) among children aged ≤5 years, as well as ≥90% coverage with hepatitis B birth dose (HepB-BD) and 3 doses of hepatitis B vaccine (HepB3) (4,5). This report describes global progress toward elimination of MTCT of HBV during 2016-2021. By December 2020, 190 (98%) of 194 World Health Organization (WHO) member states* had introduced universal infant vaccination with hepatitis B vaccine (HepB), and 110 (57%) countries provided HepB-BD to all newborns. During 2016-2020, global HepB3 coverage remained between 82% and 85%, whereas HepB-BD coverage increased from 37% to 43%. In 2020, among the 99 countries reporting both HepB3 and HepB-BD coverage, 41 (41%) achieved ≥90% coverage with both. By December 2021, serosurveys documented ≤0.1% HBsAg prevalence among children in 11 countries. Accelerating HepB-BD introduction, increasing HepB3 coverage, and monitoring programmatic and impact indicators are essential for elimination of MTCT of HBV.
Chronic Conditions Among Adults Aged 18─34 Years — United States, 2019
Authors: Kathleen B. Watson, Susan A. Carlson, Fleetwood Loustalot, Machell Town, Paul I. Eke, Craig W. Thomas, Kurt J. Greenlund
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

Chronic conditions are common, costly, and major causes of death and disability.* Addressing chronic conditions and their determinants in young adulthood can help slow disease progression and improve well-being across the life course (1); however, recent prevalence estimates examining chronic conditions in young adults overall and by subgroup have not been reported. CDC analyzed data from the Behavioral Risk Factor Surveillance System (BRFSS) to measure prevalence of 11 chronic conditions among adults aged 18-34 years overall and by selected characteristics, and to measure prevalence of health-related risk behaviors by chronic condition status. In 2019, more than one half (53.8%) of adults aged 18-34 years reported having at least one chronic condition, and nearly one quarter (22.3%) reported having more than one chronic condition. The most prevalent conditions were obesity (25.5%), depression (21.3%), and high blood pressure (10.7%). Differences in the prevalence of having a chronic condition were most noticeable between young adults with a disability (75.8%) and without a disability (48.3%) and those who were unemployed (62.3%) and students (45.8%). Adults aged 18-34 years with a chronic condition were more likely than those without one to report binge drinking, smoking, or physical inactivity. Coordinated efforts by public and private sectors might help raise awareness of chronic conditions among young adults and help improve the availability of evidence-based interventions, policies, and programs that are effective in preventing, treating, and managing chronic conditions among young adults (1).
Gun Carrying Among Youths, by Demographic Characteristics, Associated Violence Experiences, and Risk Behaviors — United States, 2017–2019
Authors: Thomas R. Simon, Heather B. Clayton, Linda L. Dahlberg, Corinne David-Ferdon, Greta Kilmer, Colleen Barbero
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

Suicide and homicide are the second and third leading causes of death, respectively, among youths aged 14-17 years (1); nearly one half (46%) of youth suicides and most (93%) youth homicides result from firearm injuries (1). Understanding youth gun carrying and associated outcomes can guide prevention initiatives (2). This study used the updated measure of gun carrying in the 2017 and 2019 administrations of CDC's Youth Risk Behavior Survey* (YRBS) to describe the national prevalence of gun carrying for reasons other than hunting or sport among high school students aged <18 years and to examine the associations between gun carrying and experiencing violence, suicidal ideation or attempts, or substance use. Gun carrying during the previous 12 months was reported by one in 15 males and one in 50 females. Gun carrying was significantly more likely among youths with violence-related experiences (adjusted prevalence ratio [aPR] range = 1.5-10.1), suicidal ideation or attempts (aPR range = 1.8-3.5), or substance use (aPR range = 4.2-5.6). These results underscore the importance of comprehensive approaches to preventing youth violence and suicide, including strategies that focus on preventing youth substance use and gun carrying (3).
Safety Monitoring of COVID-19 mRNA Vaccine Second Booster Doses Among Adults Aged ≥50 Years — United States, March 29, 2022–July 10, 2022
Authors: Anne M. Hause, James Baggs, Paige Marquez, Winston E. Abara, Jane Baumblatt, Phillip G. Blanc, John R. Su, Brandon Hugueley, Casey Parker, Tanya R. Myers, Julianne Gee, Tom T. Shimabukuro, David K. Shay
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

The Advisory Committee on Immunization Practices (ACIP) recommends that all persons aged ≥5 years receive 1 booster dose of a COVID-19 vaccine after completion of their primary series.* On March 29, 2022, the Food and Drug Administration (FDA) authorized a second mRNA booster dose ≥4 months after receipt of a first booster dose for adults aged ≥50 years and persons aged ≥12 years with moderate to severe immunocompromise (1,2). To characterize the safety of a second mRNA booster dose among persons aged ≥50 years, CDC reviewed adverse events and health impact assessments reported to v-safe and the Vaccine Adverse Event Reporting System (VAERS) after receipt of a second mRNA booster dose during March 29-July 10, 2022. V-safe is a voluntary smartphone-based U.S. active surveillance system that monitors adverse events occurring after COVID-19 vaccination. VAERS is a U.S. passive surveillance system for monitoring adverse events after vaccination, managed by CDC and FDA (3). During March 29-July 10, 2022, approximately 16.8 million persons in the United States aged ≥50 years received a fourth dose.† Among 286,380 v-safe registrants aged ≥50 years who reported receiving a second booster of an mRNA vaccine, 86.9% received vaccines from the same manufacturer for all 4 doses (i.e., homologous vaccination). Among registrants who reported homologous vaccination, injection site and systemic reactions were less frequent after the second booster dose than after the first booster dose. VAERS received 8,515 reports of adverse events after second mRNA booster doses among adults aged ≥50 years, including 8,073 (94.8%) nonserious and 442 (5.1%) serious events. CDC recommends that health care providers and patients be advised that local and systemic reactions are expected after a second booster dose, and that serious adverse events are uncommon.
Minimal invasiveness in the reconstructive treatment of peri‐implantitis defects
Authors: Eduardo Montero, Andrea Roccuzzo, Ana Molina, Alberto Monje, David Herrera, Mario Roccuzzo
Journal: Periodontology 2000 (2022)

Abstract Peri‐implantitis is a plaque‐associated pathologic condition occurring in tissues around dental implants, clinically characterized by increased peri‐implant probing pocket depth and progressive loss of supporting bone. Consequently, to arrest further disease progression and to increase the chance to obtain re‐osseointegration, surgical reconstructive procedures have been adopted. In particular, following a paradigm gathered from periodontal therapy, recent protocols have underlined the importance of a minimally invasive approach to optimize the outcomes of therapy while minimizing the risks of postoperative complications. The present review summarizes the level of evidence on the surgical reconstructive protocols focusing on the new approaches aiming to minimize surgical trauma and patients’ postoperative discomfort, underlining the pros and cons of each treatment modality.
Olfactory swab sampling optimization for α-synuclein aggregate detection in patients with Parkinson’s disease
Authors: Matilde Bongianni, Mauro Catalan, Daniela Perra, Elena Fontana, Francesco Janes, Claudio Bertolotti, Luca Sacchetto, Stefano Capaldi, Matteo Tagliapietra, Paola Polverino, Valentina Tommasini, Giulia Bellavita, Elham Ataie Kachoie, Roberto Baruca, Andrea Bernardini, Mariarosaria Valente, Michele Fiorini, Erika Bronzato, Stefano Tamburin, Laura Bertolasi, Lorenzo Brozzetti, Maria Paola Cecchini, Gianluigi Gigli, Salvatore Monaco, Paolo Manganotti, Gianluigi Zanusso
Journal: Translational Neurodegeneration (2022)

In patients with Parkinson's disease (PD), real-time quaking-induced conversion (RT-QuIC) detection of pathological α-synuclein (α-syn) in olfactory mucosa (OM) is not as accurate as in other α-synucleinopathies. It is unknown whether these variable results might be related to a different distribution of pathological α-syn in OM. Thus, we investigated whether nasal swab (NS) performed in areas with a different coverage by olfactory neuroepithelium, such as agger nasi (AN) and middle turbinate (MT), might affect the detection of pathological α-syn.NS was performed in 66 patients with PD and 29 non-PD between September 2018 and April 2021. In 43 patients, cerebrospinal fluid (CSF) was also obtained and all samples were analyzed by RT-QuIC for α-syn.In the first round, 72 OM samples were collected by NS, from AN (NSAN) or from MT (NSMT), and 35 resulted positive for α-syn RT-QuIC, including 27/32 (84%) from AN, 5/11 (45%) from MT, and 3/29 (10%) belonging to the non-PD patients. Furthermore, 23 additional PD patients underwent NS at both AN and MT, and RT-QuIC revealed α-syn positive in 18/23 (78%) NSAN samples and in 10/23 (44%) NSMT samples. Immunocytochemistry of NS preparations showed a higher representation of olfactory neural cells in NSAN compared to NSMT. We also observed α-syn and phospho-α-syn deposits in NS from PD patients but not in controls. Finally, RT-QuIC was positive in 22/24 CSF samples from PD patients (92%) and in 1/19 non-PD.In PD patients, RT-QuIC sensitivity is significantly increased (from 45% to 84%) when NS is performed at AN, indicating that α-syn aggregates are preferentially detected in olfactory areas with higher concentration of olfactory neurons. Although RT-QuIC analysis of CSF showed a higher diagnostic accuracy compared to NS, due to the non-invasiveness, NS might be considered as an ancillary procedure for PD diagnosis.
Multiplex Epstein-Barr virus BALF2 genotyping detects high-risk variants in plasma for population screening of nasopharyngeal carcinoma
Authors: Jacob A. Miller, Malaya K. Sahoo, Fumiko Yamamoto, ChunHong Huang, Hannah Wang, James L. Zehnder, Quynh-Thu Le, Benjamin A. Pinsky
Journal: Molecular Cancer (2022)

Abstract Background Epstein-Barr Virus (EBV)-associated nasopharyngeal carcinoma (NPC) exhibits unusual geographic restriction despite ubiquitous lifelong infection. Screening programs can detect most NPC cases at an early stage, but existing EBV diagnostics are limited by false positives and low positive predictive value (PPV), leading to excess screening endoscopies, MRIs, and repeated testing. Recent EBV genome-wide association studies (GWAS) suggest that EBV BALF2 variants account for more than 80% of attributable NPC risk. We therefore hypothesized that high-risk BALF2 variants could be readily detected in plasma for once-lifetime screening triage. Methods We designed and validated a multiplex genotyping assay to detect EBV BALF2 polymorphisms in human plasma. Targeted next-generation sequencing was used to validate this assay, conduct association studies with clinical phenotype, and longitudinally genotype plasma to assess within-host haplotype stability. We examined the association between NPC and BALF2 haplotypes in a large non-endemic population and three prior EBV GWAS. Finally, we estimated NPC mortality reduction, resource utilization, and cost-effectiveness of BALF2 variant-informed screening using a previously-validated cohort model. Results Following analytical validation, the BALF2 genotyping assay had 99.3% concordance with sequencing in a cohort of 24 NPC cases and 155 non-NPC controls. BALF2 haplotype was highly associated with NPC in this non-endemic population (I613V: odds ratio [OR] 7.9; V317M: OR 178.8). No other candidate BALF2 polymorphisms were significantly associated with NPC or hematologic disorders. Longitudinal genotyping revealed 97.8% within-host haplotype concordance, indicative of lifelong latent infection. In a meta-analysis of 755 NPC cases and 981 non-NPC controls, BALF2 I613V and V317M were significantly associated with NPC in both endemic and non-endemic populations. Modeled variant-informed screening strategies achieved a 46% relative increase in PPV with 7% decrease in effective screening sensitivity, thereby averting nearly half of screening endoscopies/MRIs among endemic populations in east/southeast Asia. Conclusions EBV BALF2 haplotypes are temporally stable within hosts and can be readily detected in plasma via an inexpensive multiplex genotyping assay that offers near-perfect sequencing concordance. In endemic and non-endemic populations, I613V and V317M were highly associated with NPC and could be leveraged to develop variant-informed screening programs that mitigate false positives with small reductions in screening sensitivity.
Interfacing Perforated Eardrums with Graphene‐Based Membranes for Broadband Hearing Recovery
Authors: Chunyan Li, Zhiyuan Xiong, Lei Zhou, Weiluo Huang, Yushi He, Linpeng Li, Haibo Shi, Jiayu Lu, Jian Wang, Dan Li, Shankai Yin
Journal: Advanced Healthcare Materials (2022)

Eardrum perforation and associated hearing loss is a global health problem. Grafting perforated eardrum with autologous tissues in clinic can restore low-frequency hearing but often leaves poor recovery of high-frequency hearing. In this study, the potential of incorporating a thin multilayered graphene membrane (MGM) into the eardrum for broadband hearing recovery in rats is examined. The MGM shows good biocompatibility and biostability to promote the growth of eardrum cells in a regulated manner with little sign of tissue rejection and inflammatory response. After three weeks of implantation, the MGM is found to be encapsulated by a thin layer of newly grown tissue on both sides without a significant folded overgrowth that is often seen in natural healing. The perforation is well sealed, and broadband hearing recovery (1-32 kHz) is enabled and maintained for at least 2 months. Mechanical simulations show that the high elastic modulus of MGM and thin thickness of the reconstructed eardrum play a critical role in the recovery of high-frequency hearing. This work demonstrates the promise of the use of MGM as a functional graft for perforated eardrum to recover hearing in the broadband frequency region and suggests a new acoustics-related medical application for graphene-related 2D materials.
Tom Nolan’s research reviews—28 July 2022
Authors: Tom Nolan
Journal: BMJ (2022)

<h3>Background:</h3> White matter hyperintensities in MRI scans are age related but appear to be more prevalent in depressed patients. They may be more pronounced in late onset depression. This finding, if confirmed, would potentially illuminate the heterogeneity of depression in elderly subjects. <h3>Methods:</h3> We conducted a systematic literature search of studies investigating white matter changes in late life depression, identifying 98 studies. The 30 remaining eligible studies were scrutinised for the presence and severity measures of periventricular and deep white matter changes in late life, late onset and, if available, early onset depression as well as in controls. Comparisons between groups were entered into random effects meta-analyses using odds ratios and Cohen’s d, as appropriate. Correlations with potential confounders, such as age difference between groups, were explored. <h3>Results:</h3> Late life depression and, to a greater extent, late onset depression in late life were characterised by more frequent and intense white matter abnormalities. In particular, the odds of having white matter changes were over 4 for late compared with early onset depression. Similarly, on severity scales, late onset depression had scores of 0.7–0.8 standard deviations above early onset patients. <h3>Conclusions:</h3> Significant differences between early and late onset depression suggest different aetiological mechanisms, in accordance with a theory of “cerebrovascular” depression of late onset. Greater duration of depressive symptoms, signs and treatment does not appear to have a measurable impact on white matter signal in MRI scans.
Identification of proliferative and non-proliferative subpopulations of leukemic cells in CLL
Authors: Kirsty M. Cuthill, Yan Zhang, Andrea Pepper, Lies Boelen, Eve Coulter, Becca Asquith, Stephen Devereux, Derek C. Macallan
Journal: Leukemia (2022)

Abstract Pathogenesis in chronic lymphocytic leukemia (CLL) is strongly linked to the potential for leukemic cells to migrate to and proliferate within lymph-nodes. Previous in vivo studies suggest that all leukemic cells participate in cycles of migration and proliferation. In vitro studies, however, have shown heterogeneous migration patterns. To investigate tumor subpopulation kinetics, we performed in vivo isotope-labeling studies in ten patients with IgVH -mutated CLL (M-CLL). Using deuterium-labeled glucose, we investigated proliferation in sub-populations defined by CXCR4/CD5 and surface (sIgM) expression. Mathematical modeling was performed to test the likelihood that leukemic cells exist as distinct sub-populations or as a single population with the same proliferative capacity. Further labeling studies in two patients with M-CLL commencing idelalisib investigated the effect of B-cell receptor (BCR) antagonists on sub-population kinetics. Modeling revealed that data were more consistent with a model comprising distinct sub-populations ( p = 0.008) with contrasting, characteristic kinetics. Following idelalisib therapy, similar labeling suppression across all sub-populations suggested that the most proliferative subset is the most sensitive to treatment. As the quiescent sub-population precedes treatment, selection likely explains the persistence of such residual non-proliferating populations during BCR-antagonist therapy. These findings have clinical implications for discontinuation of long-term BCR-antagonist treatment in selected patients.
LRRC8A critically regulates myofibroblast phenotypes and fibrotic remodeling following myocardial infarction
Authors: Xiyao Chen, Fuyang Zhang, Guangyu Hu, Xing Li, Lin Wang, Congye Li, Cong Huo, Rong Xu, Liming Hou, Ning Wang, Xiaoming Wang
Journal: Theranostics (2022)

Rationale: The transformation of fibroblasts into activated myofibroblasts is a critical step that results in cardiac fibrosis upon myocardial infarction (MI). Leucine-rich repeat-containing protein-8A (LRRC8A) is a multi-functional protein involved in cell survival, growth, and proliferation, whereas its role in regulating myofibroblast phenotypes and myocardial fibrosis remains unknown. Methods: Conditional myofibroblast-specific Lrrc8a knockout mouse models were established by crossing the Lrrc8aflox/flox mice with the tamoxifen-inducible periostin-Cre transgenic mice. The involvement of LRRC8A in regulating cardiac fibrosis post-MI and myofibroblast phenotypes induced by transforming growth factor-β1 (TGF-β1) was comprehensively evaluated. The mechanisms underlying LRRC8A regulation of myofibroblast phenotypes were determined by RNA sequencing-driven analysis followed by cause-effect experiments. Results: LRRC8A expression was significantly elevated in the fibrotic tissues and the fibroblasts isolated from the post-MI hearts. Compared with the wild-type (WT) littermates, the specific knockout of LRRC8A in myofibroblasts greatly attenuated myofibroblast transformation, fibrotic remodeling, and ventricular dysfunction after MI. Silencing of LRRC8A expression suppressed, whereas overexpression of LRRC8A enhanced, the pro-fibrotic myofibroblast phenotypes in isolated cardiac fibroblasts upon stimulation with TGF-β1. LRRC8A participated in TGF-β1-induced myofibroblast transformation via activating JAK2-STAT3 signaling. Furthermore, LRRC8A activated the JAK2-STAT3 pathway via its C-terminal leucine-rich repeat-domain (LRRD), directly interacting with growth factor receptor-bound protein 2 (GRB2), an adaptor protein associated with and necessary for tyrosine-phosphorylated JAK2. Conclusions: LRRC8A regulates myofibroblast transformation and cardiac fibrosis following MI. LRRC8A inhibition might be a promising strategy for cardiac fibrosis and heart failure.
Postnatal Dexamethasone Therapy Impairs Brown Adipose Tissue Thermogenesis and Autophagy Flux in Neonatal Rat Pups
Authors: Yu-Shan Chang, Shun-Yun Hou, Shang-Shiuan Yu, Shin-Yu Tsai, Ying-Yi Chen, Li-Jin Hsu, Pei-Jane Tsai, Hui-Kuan Lin, Chyi-Her Lin, Yau-Sheng Tsai
Journal: Theranostics (2022)

Rationale: Very preterm infants may require dexamethasone (Dex) for facilitating extubation or treating bronchopulmonary dysplasia. However, Dex may result in disturbance of metabolisms. This study was to investigate the effects of postnatal short course Dex exposure on brown adipose tissue (BAT) in neonatal rats. Method: Neonatal rats received either three consecutive doses of daily Dex (0.2 mg/kg/day) or saline from postnatal P1 to P3. We investigated the effects of Dex on BAT including thermogenesis, mitochondrial dynamics and autophagy flux. We also compared diurnal temperature variation between preterm infants who received systemic corticosteroid and their treatment-naïve controls. Results: Postnatal Dex treatment induced growth retardation, BAT whitening, UCP1 downregulation and cold intolerance in neonatal rats. BAT mitochondria were damaged, evident by loss of normal number, structure, and alignment of cristae. Mitochondrial fission-fusion balance was disrupted and skewed toward increased fusion, reflected by increased OPA1 and MFN2 and decreased DRP1, FIS1 and phosphorylated MFF protein levels. Autophagosome synthesis was increased but clearance was inhibited, indicated by accumulation of p62 protein after Dex treatment and no further increase of LC3-II after chloroquine co-treatment. While autophagy modulators, including chloroquine and rapamycin, did not improve UCP1 downregulation and BAT whitening, AMPK activators could partially rescue these damages. We also demonstrated that preterm infants had higher diurnal temperature variation during corticosteroid treatment. Conclusions: Postnatal short course Dex impaired BAT mitochondrial function and autophagy flux in rat pups. AMPK activators had the potential to rescue the damage.
Multiple functions of MLKL in liver fibrosis, from necroptosis to hepatic stellate cell activation
Authors: Valeria Pistorio, Chantal Housset, Jérémie Gautheron
Journal: Theranostics (2022)

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not.The documents may come from teaching and research institutions in France or abroad, or from public or private research centers.L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés. Multiple functions of MLKL in liver fibrosis, from necroptosis to hepatic stellate cell activation